The present invention is directed to compositions useful for the treatment of burns, particularly compositions and their method and environment of use including a weak acid in a gel-like carrier evidencing a demonstrated efficacy in ameliorating the sensation of pain.
Burns due to skin contact with flame, hot surfaces, hot liquids etc. are among the three most common accidents, both at the workplace and at home. The effective treatment of burn injuries continues to be a significant concern in the medical field. In North America, it is estimated that about 95% of all burn injuries are treated by home remedies, 2.5 million subjects seek medical advice for burns annually in the US., with about 100,000 of these requiring hospitalization [W.F., Am. Physician, :1321, 1992].
European figures are similar, with about 5% of burn injuries that come to medical attention admitted to hospital and a mortality rate of 0.2% [Jonsson Gynaecol :168, 1980; Hytonen Gynaecol :218, 1987; de, Burns, :58, 1994]. Most of the burn injuries occur at home, and are essentially scalding accidents with gender and age distributions varying widely by region, urbanization and education. These figures do not include sunburn injury.
The psycho-social impact of burn injuries is dramatic. Over 95% of the costs are incurred by severe injuries, mostly (xcx9ctwo thirds) in terms of lost working days and to a lesser extent for direct care [de, Ann. Acad. Med. Singapore, :680, 1994; Hansbrough, J. Burn Care Rehabil :377, 1995]. There are, however, essentially no published data that analyze the epidemiology and impact of burn injuries which do not reach medical attention, but which often do cause loss of working days and considerable, if transient reductions in quality of life [Miller, Physician, :167, 1977; Mertens North Am., :343, 1997].
The main immediate burn injury problems include pain and primary infection. Scarring and functional impairment characterize the intermediate term. Malignancy represents a long term risk, although this is rare for most burns except those from ultraviolet and other radiation. Beyond the well known misery of burn pains, the objective threats, severity and prognosis of burn injuries are all functions of injury extent, i.e. surface area and depth of tissue destruction.
The total tissue destruction is the sum of cells directly destroyed by heat and the much larger number of cells dying due to local tissue responses including edema, leukocytic infiltration, local mediators, apoptosis and primary infection. These elements are fundamental and similar in small as well as massive burn injuries, the latter adding systemic responses in a critical care scenario with mortality rates increasing as a quantitative function of tissue loss, infection and post-burn immunosuppression.
The principles of burn therapy have changed little over the past decades, and there is some lack of basic science and animal models for in depth analysis of the cellular and molecular events following tissue burn injury. There is long-standing consensus for rapid and aggressive intervention following burn injury, including the early use of skin grafting. One conclusion from this recognized need for rapid intervention is that following the direct tissue destruction by the hyperthermal insult, it is local and systemic biological responses that determine much of the post-injury course.
This scenario is analogous to, and may include, the development of shock syndromes which can be by themselves life threatening, independently of the nature and extent of a given injury [Cason, Pediatr. Surg., :3, 1981]. Other than shock, however, the immediate interference with tissue injury responses following thermotrauma has received little attention beyond general pain relief and precaution against infection [Baxter, C. R. and Waeckerle :1305, 1988; Brofeldt, J. Burn Care Rehabil., :63, 1989]. Secondary cell death due to tissue burn injury responses involves the elements of acute phase reactants such as leukocyte extravasation and mediator release. Vasoconstriction occurs peripheral to the injury locus but hyperemia and fluid loss within the injured area conspire to reduce oxygenation, accumulate toxic detritus, and activate complement and apoptosis pathways for pronounced secondary cell death. These events create the vicious circle characteristic of even small burn injuries and their misery [Shaw, A, Br. J. Hosp. Med., :583, 1994; Arturson , G., Burns, :255, 1996].
In addition, the injured tissue represents an ideal, immunologically underprivileged target site for infectious agents which can dramatically threaten the recovery process. While the need to cover burn injuries has long been recognized, ideal solutions are still elusive, and the variety of proposed remedies is profuse, ranging from honey, tree bark and animal urine or dung to potato peels to amniotic membranes, allografts and modern plastics to name but a few.
The use of tannic acids (TA) (or tannic herb extracts) as a burn remedy had been proposed early this century [Davidson, E. C., Surg. Gynecol. Obstet., 1925] based upon ancient Chinese texts. TA is the collective name for a group of undefined substances which convert putrefiable hide or skin into imputrescible leather. TA occurs in most parts of the vegetable kingdom and is more prevalent among the higher plants, especially in the barks of trees (cited from: Hupkens, Burns, :57, 1995). The acidity of these extracts is uncertain, as hydroxy groups from the trihydroxybenzene structure are extremely weak proton donors. The often ill described tannic herb extracts differed in their hepatotoxicity and tendency towards secondary infection [Hupkens, 1995]. TA treatment has been linked to liver necrosis in burn patients and even death: in one report 14 of 16 TA-treated patients who died from their burn trauma showed definitive evidence of serious liver necrosis (reviewed in [Hupkens, 1995]). This level of toxicity is unacceptable and has lead to the disappearance of TA from medical practice, although the burn toxins (a 70 year old concept no longer acceptable) released in the wound and relied on TA s ability to absorb/precipitate these putative toxins.
The use of vinegar as an antimicrobial agent is as old as the use of alcohol, and by around 1000 AD, hand washing with vinegar was recommended in ancient medical texts from China and Arabic sources such as (1031-1095 AD) [Chan, Nephrol :295, 1994].
Vinegar is an impure organic acid and a rich source of many volatile contaminants [De, Food Add. Contam 161, 1987]. It has possible antibacterial and antiviral effects, although the mechanisms of this vinegar activity is unknown. Vinegar is approved for human non-dietary use and performs well as the main ingredient of vaginal douches although mechanisms are, again, uncertain [Brinton Gynecol :49, 1990; Nyirjesy, Obstet. Gynecol :50, 1997]. The effectiveness of pure acetic acid, sodium acetate and vinegar have rarely been compared [Brighenti :242, 1995], and never with respect to antimicrobial activity. Although sodium acetate is used in some vaginal douches, their effectiveness has not been measured [Chvapil, Obstet. Gynecol :88, 1978]. While acid sensitivity of bacteria is one element of antimicrobial activity, this is insufficient to explain the antimicrobial effects of vinegar, since some common food-borne bacteria are highly sensitive to vinegar, yet they survive gastric acid exposure and cause common intestinal disease [Nishikawa, Int. J. Food Microbiol., :271, 1993]. There is a considerable amount of published literature on the antimicrobial effects of vinegar [Larghi. Argent. Microbiol :86, 1975; Fasanella, Ophthalmic. Surg., 1991; Karapinar S. A., Int. J. Food Microbiol :261, 1992; Nishikawa Ostomy. Wound Manage., :18, 1996], observations that are finding their way into the food processing industries [Dickens :576, 1994; Entani Kansenshogaku Zasshi :443, 1997]. While vinegar treatment of killed chicken prior to freezing was shown to significantly reduce bacterial contamination, there are no published reports on the effects of vinegar on living skin [Dickens, 1994]. A widely employed skin application of vinegar occurs in the Pacific Rim Countries where, acting as a nematocyst inhibitor, vinegar is the recommended first aid treatment against potentially life threatening jelly fish stings [Fenner, Med. J. Aust., :550, 1985; Beadnell Med. J. Aust., :655, 1992; Fenner, Med. J. Aust., :498, 1993]. In vitro tissue culture studies suggested that acetic acid is toxic to human fibroblasts and keratinocytes in concentrations of above 0.025% (reviewed in [C.R., 1996]). These data contrast with the frequent use of vinegar douches, which are tolerated well and over prolonged periods of intravaginal use [Nyirjesy, Obstet. Gynecol :50, 1997].
U.S. Pat. No. 5,902,600 discloses a wound dressing of glycerin polyacrylate gel.
U.S. Pat. No. 5,674,912 relates to a sunscreen and wound healing composition of pyruvic acid and various fatty acids.
U.S. Pat. No. 5,616,619 provides a burn treatment paste containing salt and lemon juice.
U.S. Pat. No. 5,560,916 is illustrative of an anti-aging dermatological composition of vinegar in a gel matrix.
U.S. Pat. No. 5,362,488 teaches a buffered skin or diaper rash cream containing a silicone polymer including citrate, citric acid and additional ingredients.
U.S. Pat. No. 5,271,943 is drawn to a wound treatment gel of salt and guar or locust gum.
U.S. Pat. No. 4,948,575 describes an alginate hydrogel foam with acetic acid and metal salts.
U.S. Pat. No. 2,338,416 describes a sunburn preparation containing aloin, agar, benzoic acid and glycerin.
The prior art fails to disclose a composition and method for its step-wise production wherein particular gelling agents, in combination with specific amounts of a pain reducing effective amount of a weak acid, e.g. acetic acid, citric acid or a combination thereof, and optionally in the presence of EDTA, are manufactured in accordance with particular production parameters which result in a particularly efficacious pain reducing dressing.
The present invention provides a composition containing a weak acid blended according to particular process parameters within a gel-like carrier. The gel may be used alone, e.g. in its gelled form or in the form of a spray. It is also within the scope of the instant invention to form various articles which demonstrate the efficacious properties of the gel composition manifested in the form of a wound dressing, an absorbent bandage, a feminine hygiene product, a diaper, or the like.
Accordingly, it is a primary objective of the present invention to provide compositions for the treatment of skin injuries, primarily burns or similar burn-like irritations.
It is a further objective of the present invention to provide a composition for treating burns comprising a therapeutically effective amount of one or more weak organic acids.
It is yet another objective of the invention to select the therapeutically effective organic acids from a group including, but not limited to, acetic acid, vinegar, citric acid or combinations thereof, in a pharmacologically effective carrier, wherein the pH of the composition ranges from about 2.5 to 4.5.
It is still an additional objective of the instant invention to provide a kit for the treatment of burns comprising:
a composition for treating burns comprising a therapeutically effective amount of one or more weak organic acids as defined supra, said acids being incorporated within a pharmacologically effective carrier, and wherein the pH of the composition ranges from about 2.5 to 4.5;
wrapping or bandage materials; and
instructions for use.
It is yet another objective of the invention to provide a pharmacologically effective carrier for the acid which is in the form of an aqueous based carrier, preferably a gel form, utilizing a CARBOPOL gelling agent or equivalent.
It is a still further embodiment of the invention to include one or more additional agents, incorporated within the acid containing gel matrix, said agents including, but not limited to sun blocking agents, skin moisturizing agents, herb extracts and antimicrobial agents.
It is a still further objective of the invention to teach a method for treating skin trauma arising from sources including, but not limited to thermal, chemical, light sources, or the like wherein the method includes application to the affected area of the skin of a therapeutically effective amount of an acid containing gel as described supra, wherein the pH ranges from about 2.5 to 4.5, preferably between 4.1 and 4.4, most preferably 4.15 to 4.25, and optimally at 4.2.
It is still an additional objective of the instant invention to provide a form of skin treatment effective to provide sustained localized concentrations of H+ ions.
It is a further objective of the instant invention to mediate the perception of pain by providing effective intervention within the nociceptor pathways.
It is still another objective of the instant invention to provide a composition and process for promoting scar-less wound healing.
Other objects and advantages of this invention will become apparent from the following description taken in conjunction with the accompanying drawings wherein are set forth, by way of illustration and example, certain embodiments of this invention. The drawings constitute a part of this specification and include exemplary embodiments of the present invention and illustrate various objects and features thereof.